Immune NetworkPub Date : 2023-02-21eCollection Date: 2023-02-01DOI: 10.4110/in.2023.23.e3
Hye-Ran Kim, Jeong-Su Park, Won-Chang Soh, Na-Young Kim, Hyun-Yoong Moon, Ji-Su Lee, Chang-Duk Jun
{"title":"T Cell Microvilli: Finger-Shaped External Structures Linked to the Fate of T Cells.","authors":"Hye-Ran Kim, Jeong-Su Park, Won-Chang Soh, Na-Young Kim, Hyun-Yoong Moon, Ji-Su Lee, Chang-Duk Jun","doi":"10.4110/in.2023.23.e3","DOIUrl":"10.4110/in.2023.23.e3","url":null,"abstract":"<p><p>Microvilli are outer membrane organelles that contain cross-linked filamentous actin. Unlike well-characterized epithelial microvilli, T-cell microvilli are dynamic similar to those of filopodia, which grow and shrink intermittently via the alternate actin-assembly and -disassembly. T-cell microvilli are specialized for sensing Ags on the surface of Ag-presenting cells (APCs). Thus, these finger-shaped microprotrusions contain many signaling-related proteins and can serve as a signaling platforms that induce intracellular signals. However, they are not limited to sensing external information but can provide sites for parts of the cell-body to tear away from the cell. Cells are known to produce many types of extracellular vesicles (EVs), such as exosomes, microvesicles, and membrane particles. T cells also produce EVs, but little is known about under what conditions T cells generate EVs and which types of EVs are released. We discovered that T cells produce few exosomes but release large amounsts of microvilli-derived particles during physical interaction with APCs. Although much is unanswered as to why T cells use the same organelles to sense Ags or to produce EVs, these events can significantly affect T cell fate, including clonal expansion and death. Since TCRs are localized at microvilli tips, this membrane event also raises a new question regarding long-standing paradigm in T cell biology; i.e., surface TCR downmodulation following T cell activation. Since T-cell microvilli particles carry T-cell message to their cognate partner, these particles are termed T-cell immunological synaptosomes (TISs). We discuss the potential physiological role of TISs and their application to immunotherapies.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 1","pages":"e3"},"PeriodicalIF":4.3,"publicationDate":"2023-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b0/aa/in-23-e3.PMC9995986.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9455871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2023-02-20eCollection Date: 2023-02-01DOI: 10.4110/in.2023.23.e11
Joon Seok, Sung-Dong Cho, Seong Jun Seo, Su-Hyung Park
{"title":"Roles of Virtual Memory T Cells in Diseases.","authors":"Joon Seok, Sung-Dong Cho, Seong Jun Seo, Su-Hyung Park","doi":"10.4110/in.2023.23.e11","DOIUrl":"10.4110/in.2023.23.e11","url":null,"abstract":"<p><p>Memory T cells that mediate fast and effective protection against reinfections are usually generated upon recognition on foreign Ags. However, a \"memory-like\" T-cell population, termed virtual memory T (T<sub>VM</sub>) cells that acquire a memory phenotype in the absence of foreign Ag, has been reported. Although, like innate cells, T<sub>VM</sub> cells reportedly play a role in first-line defense to bacterial or viral infections, their protective or pathological roles in immune-related diseases are largely unknown. In this review, we discuss the current understanding of T<sub>VM</sub> cells, focusing on their distinct characteristics, immunological properties, and roles in various immune-related diseases, such as infections and cancers.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 1","pages":"e11"},"PeriodicalIF":4.3,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/72/cb/in-23-e11.PMC9995991.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9455873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2023-02-17eCollection Date: 2023-02-01DOI: 10.4110/in.2023.23.e4
Gap Ryol Lee
{"title":"Molecular Mechanisms of T Helper Cell Differentiation and Functional Specialization.","authors":"Gap Ryol Lee","doi":"10.4110/in.2023.23.e4","DOIUrl":"10.4110/in.2023.23.e4","url":null,"abstract":"<p><p>Th cells, which orchestrate immune responses to various pathogens, differentiate from naïve CD4 T cells into several subsets that stimulate and regulate immune responses against various types of pathogens, as well as a variety of immune-related diseases. Decades of research have revealed that the fate decision processes are controlled by cytokines, cytokine receptor signaling, and master transcription factors that drive the differentiation programs. Since the Th1 and Th2 paradigm was proposed, many subsets have been added to the list. In this review, I will summarize these events, including the fate decision processes, subset functions, transcriptional regulation, metabolic regulation, and plasticity and heterogeneity. I will also introduce current topics of interest.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 1","pages":"e4"},"PeriodicalIF":4.3,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d0/dc/in-23-e4.PMC9995992.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9455872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2023-02-16eCollection Date: 2023-04-01DOI: 10.4110/in.2023.23.e16
Kee Woong Kwon, Tae Gun Kang, Ara Lee, Seung Mo Jin, Yong Taik Lim, Sung Jae Shin, Sang-Jun Ha
{"title":"Protective Efficacy and Immunogenicity of Rv0351/Rv3628 Subunit Vaccine Formulated in Different Adjuvants Against <i>Mycobacterium tuberculosis</i> Infection.","authors":"Kee Woong Kwon, Tae Gun Kang, Ara Lee, Seung Mo Jin, Yong Taik Lim, Sung Jae Shin, Sang-Jun Ha","doi":"10.4110/in.2023.23.e16","DOIUrl":"10.4110/in.2023.23.e16","url":null,"abstract":"<p><p>Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for tuberculosis (TB) prevention. Previously, our group demonstrated the vaccine potential of Rv0351 and Rv3628 against <i>Mycobacterium tuberculosis</i> (Mtb) infection by directing Th1-biased CD4<sup>+</sup> T cells co-expressing IFN-γ, TNF-α, and IL-2 in the lungs. Here, we assessed immunogenicity and vaccine potential of the combined Ags (Rv0351/Rv3628) formulated in different adjuvants as subunit booster in BCG-primed mice against hypervirulent clinical Mtb strain K (Mtb K). Compared to BCG-only or subunit-only vaccine, BCG prime and subunit boost regimen exhibited significantly enhanced Th1 response. Next, we evaluated the immunogenicity to the combined Ags when formulated with four different types of monophosphoryl lipid A (MPL)-based adjuvants: 1) dimethyldioctadecylammonium bromide (DDA), MPL, and trehalose dicorynomycolate (TDM) in liposome form (DMT), 2) MPL and Poly I:C in liposome form (MP), 3) MPL, Poly I:C, and QS21 in liposome form (MPQ), and 4) MPL and Poly I:C in squalene emulsion form (MPS). MPQ and MPS displayed greater adjuvancity in Th1 induction than DMT or MP did. Especially, BCG prime and subunit-MPS boost regimen significantly reduced the bacterial loads and pulmonary inflammation against Mtb K infection when compared to BCG-only vaccine at a chronic stage of TB disease. Collectively, our findings highlighted the importance of adjuvant components and formulation to induce the enhanced protection with an optimal Th1 response.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 2","pages":"e16"},"PeriodicalIF":6.0,"publicationDate":"2023-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/36/a9/in-23-e16.PMC10166659.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9467551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2023-02-01DOI: 10.4110/in.2023.23.e8
June-Young Koh, Dong-Uk Kim, Bae-Hyeon Moon, Eui-Cheol Shin
{"title":"Human CD8<sup>+</sup> T-Cell Populations That Express Natural Killer Receptors.","authors":"June-Young Koh, Dong-Uk Kim, Bae-Hyeon Moon, Eui-Cheol Shin","doi":"10.4110/in.2023.23.e8","DOIUrl":"https://doi.org/10.4110/in.2023.23.e8","url":null,"abstract":"<p><p>CD8<sup>+</sup> T cells are activated by TCRs that recognize specific cognate Ags, while NK-cell activation is regulated by a balance between signals from germline-encoded activating and inhibitory NK receptors. Through these different processes of Ag recognition, CD8<sup>+</sup> T cells and NK cells play distinct roles as adaptive and innate immune cells, respectively. However, some human CD8<sup>+</sup> T cells have been found to express activating or inhibitory NK receptors. CD8<sup>+</sup> T-cell populations expressing NK receptors straddle the innate-adaptive boundary with their innate-like features. Recent breakthrough technical advances in multi-omics analysis have enabled elucidation of the unique immunologic characteristics of these populations. However, studies have not yet fully clarified the heterogeneity and immunological characteristics of each CD8<sup>+</sup> T-cell population expressing NK receptors. Here we aimed to review the current knowledge of various CD8<sup>+</sup> T-cell populations expressing NK receptors, and to pave the way for delineating the landscape and identifying the various roles of these T-cell populations.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 1","pages":"e8"},"PeriodicalIF":6.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/26/ca/in-23-e8.PMC9995994.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9471676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2023-02-01DOI: 10.4110/in.2023.23.e2
Sung-Woo Lee, Gil-Woo Lee, Hee-Ok Kim, Jae-Ho Cho
{"title":"Shaping Heterogeneity of Naive CD8<sup>+</sup> T Cell Pools.","authors":"Sung-Woo Lee, Gil-Woo Lee, Hee-Ok Kim, Jae-Ho Cho","doi":"10.4110/in.2023.23.e2","DOIUrl":"https://doi.org/10.4110/in.2023.23.e2","url":null,"abstract":"<p><p>Immune diversification helps protect the host against a myriad of pathogens. CD8<sup>+</sup> T cells are essential adaptive immune cells that inhibit the spread of pathogens by inducing apoptosis in infected host cells, ultimately ensuring complete elimination of infectious pathogens and suppressing disease development. Accordingly, numerous studies have been conducted to elucidate the mechanisms underlying CD8<sup>+</sup> T cell activation, proliferation, and differentiation into effector and memory cells, and to identify various intrinsic and extrinsic factors regulating these processes. The current knowledge accumulated through these studies has led to a huge breakthrough in understanding the existence of heterogeneity in CD8<sup>+</sup> T cell populations during immune response and the principles underlying this heterogeneity. As the heterogeneity in effector/memory phases has been extensively reviewed elsewhere, in the current review, we focus on CD8<sup>+</sup> T cells in a \"naïve\" state, introducing recent studies dealing with the heterogeneity of naive CD8<sup>+</sup> T cells and discussing the factors that contribute to such heterogeneity. We also discuss how this heterogeneity contributes to establishing the immense complexity of antigen-specific CD8<sup>+</sup> T cell response.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 1","pages":"e2"},"PeriodicalIF":6.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ab/67/in-23-e2.PMC9995989.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9157319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2023-01-31eCollection Date: 2023-04-01DOI: 10.4110/in.2023.23.e15
Seungwon Ryu, Hye Young Kim
{"title":"Bone Marrow Progenitors and IL-2 Signaling Contribute to the Strain Differences of Kidney Innate Lymphoid Cells.","authors":"Seungwon Ryu, Hye Young Kim","doi":"10.4110/in.2023.23.e15","DOIUrl":"10.4110/in.2023.23.e15","url":null,"abstract":"<p><p>Innate lymphoid cells (ILCs) are critical immune-response mediators. Although they largely reside in mucosal tissues, the kidney also bears substantial numbers. Nevertheless, kidney ILC biology is poorly understood. BALB/c and C57BL/6 mice are known to display type-2 and type-1 skewed immune responses, respectively, but it is unclear whether this extends to ILCs. We show here that indeed, BALB/c mice have higher total ILCs in the kidney than C57BL/6 mice. This difference was particularly pronounced for ILC2s. We then showed that three factors contributed to the higher ILC2s in the BALB/c kidney. First, BALB/c mice demonstrated higher numbers of ILC precursors in the bone marrow. Second, transcriptome analysis showed that compared to C57BL/6 kidneys, the BALB/c kidneys associated with significantly higher IL-2 responses. Quantitative RT-PCR also showed that compared to C57BL/6 kidneys, the BALB/c kidneys expressed higher levels of IL-2 and other cytokines known to promote ILC2 proliferation and/or survival (IL-7, IL-33, and thymic stromal lymphopoietin). Third, the BALB/c kidney ILC2s may be more sensitive to the environmental signals than C57BL/6 kidney ILC2s since they expressed their transcription factor GATA-3 and the IL-2, IL-7, and IL-25 receptors at higher levels. Indeed, they also demonstrated greater responsiveness to IL-2 than C57BL/6 kidney ILC2s, as shown by their greater STAT5 phosphorylation levels after culture with IL-2. Thus, this study demonstrates previously unknown properties of kidney ILC2s. It also shows the impact of mouse strain background on ILC2 behavior, which should be considered when conducting research on immune diseases with experimental mouse models.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 2","pages":"e15"},"PeriodicalIF":4.3,"publicationDate":"2023-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/1f/in-23-e15.PMC10166654.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9838435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2023-01-30eCollection Date: 2023-04-01DOI: 10.4110/in.2023.23.e14
Young-Ju Kang, Hee Jun Cho, Yunhee Lee, Arum Park, Mi Jeong Kim, In Cheul Jeung, Yong-Wook Jung, Haiyoung Jung, Inpyo Choi, Hee Gu Lee, Suk Ran Yoon
{"title":"IL-17A and Th17 Cells Contribute to Endometrial Cell Survival by Inhibiting Apoptosis and NK Cell Mediated Cytotoxicity of Endometrial Cells via ERK1/2 Pathway.","authors":"Young-Ju Kang, Hee Jun Cho, Yunhee Lee, Arum Park, Mi Jeong Kim, In Cheul Jeung, Yong-Wook Jung, Haiyoung Jung, Inpyo Choi, Hee Gu Lee, Suk Ran Yoon","doi":"10.4110/in.2023.23.e14","DOIUrl":"10.4110/in.2023.23.e14","url":null,"abstract":"<p><p>Immune status including the immune cells and cytokine profiles has been implicated in the development of endometriosis. In this study, we analyzed Th17 cells and IL-17A in peritoneal fluid (PF) and endometrial tissues of patients with (n=10) and without (n=26) endometriosis. Our study has shown increased Th17 cell population and IL-17A level in PF with endometriosis patients. To determine the roles of IL-17A and Th17 cells in the development of endometriosis, the effect of IL-17A, major cytokine of Th17, on endometrial cells isolated from endometriotic tissues was examined. Recombinant IL-17A promoted survival of endometrial cells accompanied by increased expression of anti-apoptotic genes, including Bcl-2 and MCL1, and the activation of ERK1/2 signaling. In addition, treatment of IL-17A to endometrial cells inhibited NK cell mediated cytotoxicity and induced HLA-G expression on endometrial cells. IL-17A also promoted migration of endometrial cells. Our data suggest that Th17 cells and IL-17A play critical roles in the development of endometriosis by promoting endometrial cell survival and conferring a resistance to NK cell cytotoxicity through the activation of ERK1/2 signaling. Targeting IL-17A has potential as a new strategy for the treatment of endometriosis.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 2","pages":"e14"},"PeriodicalIF":6.0,"publicationDate":"2023-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/74/b4/in-23-e14.PMC10166657.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9467557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2023-01-27eCollection Date: 2023-04-01DOI: 10.4110/in.2023.23.e12
Min-Hee Kim, Chang-Woo Lee
{"title":"Phosphatase Ssu72 Is Essential for Homeostatic Balance Between CD4<sup>+</sup> T Cell Lineages.","authors":"Min-Hee Kim, Chang-Woo Lee","doi":"10.4110/in.2023.23.e12","DOIUrl":"10.4110/in.2023.23.e12","url":null,"abstract":"<p><p>Ssu72, a dual-specificity protein phosphatase, not only participates in transcription biogenesis, but also affects pathophysiological functions in a tissue-specific manner. Recently, it has been shown that Ssu72 is required for T cell differentiation and function by controlling multiple immune receptor-mediated signals, including TCR and several cytokine receptor signaling pathways. Ssu72 deficiency in T cells is associated with impaired fine-tuning of receptor-mediated signaling and a defect in CD4<sup>+</sup> T cell homeostasis, resulting in immune-mediated diseases. However, the mechanism by which Ssu72 in T cells integrates the pathophysiology of multiple immune-mediated diseases is still poorly elucidated. In this review, we will focus on the immunoregulatory mechanism of Ssu72 phosphatase in CD4<sup>+</sup> T cell differentiation, activation, and phenotypic function. We will also discuss the current understanding of the correlation between Ssu72 in T cells and pathological functions which suggests that Ssu72 might be a therapeutic target in autoimmune disorders and other diseases.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 2","pages":"e12"},"PeriodicalIF":6.0,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/05/da/in-23-e12.PMC10166661.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9838434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2023-01-27eCollection Date: 2023-02-01DOI: 10.4110/in.2023.23.e9
Andrea M Amitrano, Minsoo Kim
{"title":"Metabolic Challenges in Anticancer CD8 T Cell Functions.","authors":"Andrea M Amitrano, Minsoo Kim","doi":"10.4110/in.2023.23.e9","DOIUrl":"10.4110/in.2023.23.e9","url":null,"abstract":"<p><p>Cancer immunotherapies continue to face numerous obstacles in the successful treatment of solid malignancies. While immunotherapy has emerged as an extremely effective treatment option for hematologic malignancies, it is largely ineffective against solid tumors due in part to metabolic challenges present in the tumor microenvironment (TME). Tumor-infiltrating CD8<sup>+</sup> T cells face fierce competition with cancer cells for limited nutrients. The strong metabolic suppression in the TME often leads to impaired T-cell recruitment to the tumor site and hyporesponsive effector functions via T-cell exhaustion. Growing evidence suggests that mitochondria play a key role in CD8<sup>+</sup> T-cell activation, migration, effector functions, and persistence in tumors. Therefore, targeting the mitochondrial metabolism of adoptively transferred T cells has the potential to greatly improve the effectiveness of cancer immunotherapies in treating solid malignancies.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 1","pages":"e9"},"PeriodicalIF":4.3,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e6/d0/in-23-e9.PMC9995993.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9353922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}